PDF(Pubmed)
Abstract：
Many organisms utilize an actin- and myosin-based cytokinetic ring (CR) to help complete cytokinesis. In Schizosaccharomyces pombe, the Septation Initiation Network (SIN) promotes proper CR function and stability. The SIN is a conserved and essential signaling network consisting of a GTPase and a cascade of kinases assembled at the spindle pole body (SPB). The PP2A SIN inhibitory phosphatase (SIP) complex related to the STRIPAK phosphatase complex is one inhibitor of SIN signaling. The SIP consists of Csc1, Csc2, Csc3, Csc4, Paa1, and the phosphatase subunit Ppa3. Here, we determine that the SIP is anchored at the SPB via the Csc1 FHA domain and that constitutive SPB localization of the SIP is lethal due to persistent SIN inhibition. Disrupting SIP docking at the SPB with a point mutation within the FHA domain or eliminating phosphatase activity by introducing a point mutation within Ppa3 resulted in intact SIP complexes without SIN inhibitory function. Lastly, we defined the unique features of Ppa3 that allow it, but not two other PP2A catalytic subunits, to incorporate into the SIP. Overall, we provide insight into how the SIP complex assembles, localizes, and functions to counteract the SIN with spatiotemporal precision during cytokinesis.
摘要：
许多生物体利用基于肌动蛋白和肌球蛋白的细胞动力学环来帮助完成胞质分裂。在裂殖酵母中，分离起始网络(SIN)促进适当的CR功能和稳定性。SIN是一种保守且必需的信号传导网络，由GTP酶和在主轴极体（SPB）处组装的一系列激酶组成。与STRIPAK磷酸酶复合物相关的PP2ASIN抑制性磷酸酶（SIP）复合物是SIN信号传导的一种抑制剂。SIP由Csc1、Csc2、Csc3、Csc4、Paa1和磷酸酶亚基Ppa3组成。这里,我们确定SIP通过Csc1FHA结构域锚定在SPB，并且由于持续的SIN抑制，SIP的组成型SPB定位是致命的。用FHA结构域内的点突变破坏SPB处的SIP对接或通过在Ppa3内引入点突变来消除磷酸酶活性导致没有SIN抑制功能的完整SIP复合物。最后,我们定义了Ppa3的独特功能，但不是另外两个PP2A催化亚基，纳入SIP。总的来说,我们提供有关SIP复合体如何组装的见解，本地化，并在胞质分裂过程中以时空精度抵消SIN。
